Tardive dyskinesia remains a major problem in the pharmacological treatment of schizophrenia. Since no safe and effective treatment has been established, identification of risk factors and prevention is an important goal. Our objective is to continue an ongoing prospective study of tardive dyskinesia development among a large randomly selected sample of psychiatric patients. To date 777 patients have entered the study including 120 patients with no exposure to neuroleptics and 100 patients receiving fluphenazine decanoate. The median length of cumulative neuroleptic exposure at study entry is 10 months; therefore, patients are available early in their treatment course. At baseline a complete medical and neurological history, psychotropic medication history, EEG, psychometric testing and ratings on the BPRS, Simpson-Angus and Simpson Dyskinesia Scale are obtained. Subjects are reevaluated with the three rating scales every three months by raters blind to medication history. Patients with questionable signs are seen monthly. Those who develop presumptive TD are evaluated medically and neurologically, videotaped and reexamined every two weeks. (Antipsychotic medication is withdrawn on the majority of those cases.) This investigation should provide important new knowledge of incidence and course of TD, as well as an opportunity to assess a variety of possible risk factors. To date 44 cases of presumptive TD have developed, and preliminary analyses suggest that continuation of the project will be of enormous value. An additional three years will allow all patients entered to date to have a minimum follow-up of four years. The availability of a larger number of TD cases will permit more meaningful analyses of risk factors in development and persistence of TC.